Tuning of redox properties for the design of ruthenium anticancer drugs: part 2. Syntheses, crystal structures, and electrochemistry of potentially antitumor [Ru III/II Cl6-n(Azole)n]z(n = 3, 4, 6) complexes

A series of mixed chloro-azole ruthenium complexes with potential antitumor activity, viz., mer-[RuIIICl3(azole)3] (B), trans-[RuIIICl2(azole)4]Cl (C), trans-[RuIICl2(azole)4] (D), and [RuII(azole)6](SO3CF3)2 (E), where azole = 1-butylimidazole (1), imidazole (2), benzimidazole (3), 1-methyl-1,2,4-triazole (4), 4-methylpyrazole (5), 1,2,4-triazole (6), pyrazole (7), and indazole (8), have been prepared as a further development of anticancer drugs with the general formula [RuCl4(azole)2]- (A). These compounds were characterized by elemental analysis, IR spectroscopy, electronic spectra, electrospray mass spectrometry, and X-ray crystallography. The electrochemical behavior has been studied in detail in DMF, DMSO, and aqueous media using cyclic voltammetry, square wave voltammetry, and controlled potential electrolysis. Compounds B and a number of C complexes exhibit one RuIII/RuII reduction, followed, at a sufficiently long time scale, by metal dechlorination on solvolysis. The redox potential values in organic media agree with those predicted by Lever's parametrization method, and the yet unknown EL parameters were estimated for 1 (EL = 0.06 V), 3 (EL = 0.10 V), 4 (EL = 0.17 V), and 5 (EL = 0.18 V). The EL values for the azole ligands 1-8 correlate linearly with their basicity (pK(a) value of the corresponding azolium acid H2L+). In addition, a logarithmic dependence between the homogeneous rate constants for the reductively induced stepwise replacement of chloro ligands by solvent molecules and the RuIII/RuII redox potentials was observed. Lower E(1/2) values (higher net electron donor character of the ligands) result in enhanced kinetic rate constants of solvolysis upon reduction. The effect of the net charge on the RuIII/RuII redox potentials in water is tentatively explained by the application of the Born equation. In addition, the pH-dependent electrochemical behavior of trans-[RuCl2(1,2,4-triazole)4]Cl is discussed.